Mechanisms of Stroke Recovery

Introduction

The consequences of stroke can be chronically disabling and overall represents the leading cause of long-term disability . A greater understanding of the mechanisms of stroke recovery will facilitate clinical, pharmacologic, and cell-based approaches to stroke recovery and rehabilitation. The infarct core at the center of the territory of occluded artery results in the cellular death of neurons and supporting cellular elements (glial cells) and thus, ultimately, the impairment of sensory and motor function. The surviving peri-infarct zone brain region adjacent to the infarct core and connected brain regions shows heightened neuroplasticity, allowing the remapping of sensory and motor functions from damaged areas and thus promoting recovery from stroke . Mechanisms of recovery in these areas are multifaceted and hold to the inherent limitations of the endogenous cellular and molecular mechanisms involved in neural repair and to the time frame in which stroke recovery is possible. A useful framework to understand the mechanisms of stroke recovery consists of three fundamental themes: (1) timeline for stroke recovery, (2) excitatory neuronal signaling, and (3) promotion of growth programs, such as neurogenesis, oligodendrogenesis, and axonal sprouting. Here we discuss the mechanisms and time course of tissue repair after ischemic stroke.

Timeline for Stroke Recovery

Following ischemic stroke, the old adage “time heals all wounds” may not necessarily apply, but the machinery set forth by poststroke recovery events evolves with each phase of recovery. The normal course of stroke recovery can be divided into three overlapping phases: acute, subacute, and chronic.

The acute phase occurs during the initial minutes to days of the ischemic event. The initial clinical improvement occurs independent of patient behavior and physical or environmental stimulation and is attributed to the resolution of the effects of edema, diaschisis, and return of circulation within the penumbra. Edema surrounding the infarct may disrupt nearby neuronal functioning. As the edema subsides, these neurons may regain function, allowing for early recovery. The normalization of blood flow to the penumbra, the nonischemic area of low to moderate blood flow surrounding the infarct core, can facilitate early recovery by restoration of excitability and network responsiveness to previously nonfunctioning neurons. Diaschisis, the inhibition or suppression of surrounding cortical tissue or of cortical regions at a distance that are interconnected with the infarct core, may be partially resolved with reduction in edema, and neuronal function may return if the connected area of the brain is intact. Further improvement in diaschisis will continue into the subacute phase.

A few days to 3 months after the ischemic event is the subacute phase. During this period the endogenous mechanisms of neural repair are primed and engagement in rehabilitation is potentially most beneficial for stroke recovery. Patients who have had stroke exhibit most recovery from physical and sensorimotor impairments and near-plateaus on standardized scales of impairment, self-care, and mobility. Studies in humans and animal models show that most recovery from impairment during this period occurs as a result of both natural reorganization and increased responsiveness to enriched environments and training. Patients who engage in rehabilitation with repetitive practice have greater improvement in those skills (skilled use of the extremities) than in those who did not undergo practice. Beyond the 3-month period, the chronic phase, improvement on standardized impairment scale, such as the Fugl-Meyer scale, is substantially less than that seen during the subacute phase. Nevertheless, improvement can still be induced by rehabilitative therapies at this stage.